The early onset forms of periodontal disease, including juvenile (JP) and rapidly progressive (RP) periodontitis, are known to be familial disorders, but the etiology and pathogenesis are not clearly understood. Comprehensive and carefully designed family studies provide one of the most promising approaches to elucidating underlying cellular and biochemical correlates of JP and RP, as well as permitting investigation into the mode(s) of inheritance and variability of the phenotype(s). The purpose of the proposed research is to continue assembling the largest known collection of JP and RP patients, and to perform systematic and comprehensive clinical evaluations of probands and all available relatives. Neutrophil chemotaxis assays will be performed and serum antibodies to H. actinomycetemcomitans, B. gingivalis, as well as other bacteria will be determined. Possible (genetic) heterogeneity will be explored by the evaluation of demographic factors and familial variability in cellular, biochemical, and clinical parameters. Serum antibody reactivity will be correlated with clinical patterns of periodontal destruction (loss of attachment). Formal segregation analysis will be performed to test Mendelian hypotheses, and to estimate segregation ratios or transmission probabilities. Some limitations of the genetic analysis, including missing data and bias due to ascertainment, will be investigated using simulation studies. The results of these family studies will provide: (1) insight into potential methods of presymptomatic or early diagnosis; (2) clarification of variability and diagnostic categorization of these disorders; (3) determination of risk to relatives of probands; and (4) generation of hypotheses regarding potential etiologic mechanisms and genetic heterogeneity among the forms of early onset periodontitis.